Tumor-targeted supramolecular catalytic nanoreactor for synergistic chemo/chemodynamic therapy via oxidative stress amplification and cascaded Fenton reaction

2020 ◽  
Vol 390 ◽  
pp. 124628 ◽  
Author(s):  
Xiaoyu Xu ◽  
Zishan Zeng ◽  
Jie Chen ◽  
Binyao Huang ◽  
Zilin Guan ◽  
...  
Author(s):  
Jean Felix Mukerabigwi ◽  
Yu Han ◽  
Nannan Lu ◽  
Wendong Ke ◽  
Yuheng Wang ◽  
...  

Drug resistance of cisplatin significantly limits its therapeutic efficacy in clinical applications against a variety of cancers. Herein, we develop a novel strategy to overcome cisplatin drug resistance through sensitizing...


2017 ◽  
Vol 2017 ◽  
pp. 1-15 ◽  
Author(s):  
Krzysztof Michalak ◽  
Aleksandra Sobolewska-Włodarczyk ◽  
Marcin Włodarczyk ◽  
Justyna Sobolewska ◽  
Piotr Woźniak ◽  
...  

Long-term fluoroquinolone-associated disability (FQAD) after fluoroquinolone (FQ) antibiotic therapy appears in recent years as a significant medical and social problem, because patients suffer for many years after prescribed antimicrobial FQ treatment from tiredness, concentration problems, neuropathies, tendinopathies, and other symptoms. The knowledge about the molecular activity of FQs in the cells remains unclear in many details. The effective treatment of this chronic state remains difficult and not effective. The current paper reviews the pathobiochemical properties of FQs, hints the directions for further research, and reviews the research concerning the proposed treatment of patients. Based on the analysis of literature, the main directions of possible effective treatment of FQAD are proposed: (a) reduction of the oxidative stress, (b) restoring reduced mitochondrion potential ΔΨm, (c) supplementation of uni- and bivalent cations that are chelated by FQs and probably ineffectively transported to the cell (caution must be paid to Fe and Cu because they may generate Fenton reaction), (d) stimulating the mitochondrial proliferation, (e) removing FQs permanently accumulated in the cells (if this phenomenon takes place), and (f) regulating the disturbed gene expression and enzyme activity.


2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Daniel Wysokinski ◽  
Janusz Blasiak ◽  
Mariola Dorecka ◽  
Marta Kowalska ◽  
Jacek Robaszkiewicz ◽  
...  

Oxidative stress is a major factor in the pathogenesis of age-related macular degeneration (AMD). Iron may catalyze the Fenton reaction resulting in overproduction of reactive oxygen species. Transferrin receptor 2 plays a critical role in iron homeostasis and variability in its gene may influence oxidative stress and AMD occurrence. To verify this hypothesis we assessed the association between polymorphisms of theTFR2gene and AMD. A total of 493 AMD patients and 171 matched controls were genotyped for the two polymorphisms of theTFR2gene: c.1892C>T (rs2075674) and c.−258+123T>C (rs4434553). We also assessed the modulation of some AMD risk factors by these polymorphisms. The CC and TT genotypes of the c.1892C>T were associated with AMD occurrence but the latter only in obese patients. The other polymorphism was not associated with AMD occurrence, but the CC genotype was correlated with an increasing AMD frequency in subjects withBMI<26. The TT genotype and the T allele of this polymorphism decreased AMD occurrence in subjects above 72 years, whereas the TC genotype and the C allele increased occurrence of AMD in this group. The c.1892C>T and c.−258+123T>C polymorphisms of theTRF2gene may be associated with AMD occurrence, either directly or by modulation of risk factors.


2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Katarzyna A. Wójcik ◽  
Ewelina Synowiec ◽  
Manuel P. Jiménez-García ◽  
Anna Kaminska ◽  
Piotr Polakowski ◽  
...  

Oxidative stress may play a role in the pathogenesis of keratoconus (KC) and Fuchs endothelial corneal dystrophy (FECD). Iron may promote the stress by the Fenton reaction, so its homeostasis should be strictly controlled. Transferrin is essential for iron homeostasis because it transports iron from plasma into cells. The malfunction of transferrin, which may be caused by variation in its gene (TF) variation, may contribute to oxidative stress and change KC and FECD risk. To verify this hypothesis we investigated the association between three polymorphisms of theTFgene, g.3296G>A (rs8177178), g.3481A>G (rs8177179), and c.–2G>A (rs1130459), and KC and FECD occurrence. Genotyping was performed in blood lymphocytes in 216 patients with KC, 130 patients with FECD and 228 controls by PCR-RFLP. We studied also the influence of other risk factors. The A/A genotype and the A allele of the g.3296G>A polymorphism were associated with KC occurrence, while the G allele was negatively correlated with it. We observed a decrease in KC occurrence associated with the A/G genotype of the g.3481A>G polymorphism. We did not find any association between the c.–2G>A polymorphism and KC. No association was found between all three polymorphisms and FECD occurrence.


2019 ◽  
Vol 177 (2) ◽  
pp. 476-482 ◽  
Author(s):  
Alessandro Corti ◽  
Justine Bonetti ◽  
Silvia Dominici ◽  
Simona Piaggi ◽  
Vanna Fierabracci ◽  
...  

Abstract Asbestos is the main causative agent of malignant pleural mesothelioma. The variety known as crocidolite (blue asbestos) owns the highest pathogenic potential, due to the dimensions of its fibers as well as to its content of iron. The latter can in fact react with macrophage-derived hydrogen peroxide in the so called Fenton reaction, giving rise to highly reactive and mutagenic hydroxyl radical. On the other hand, hydroxyl radical can as well originate after thiol-dependent reduction of iron, a process capable of starting its redox cycling. Previous studies showed that glutathione (GSH) is one such thiol, and that cellular gamma-glutamyltransferase (GGT) can efficiently potentiate GSH-dependent iron redox cycling and consequent oxidative stress. As GGT is expressed in macrophages and is released upon their activation, the present study was aimed at verifying the hypothesis that GSH/GGT-dependent redox reactions may participate in the oxidative stress following the activation of macrophages induced by crocidolite asbestos. Experiments in acellular systems confirmed that GGT-mediated metabolism of GSH can potentiate crocidolite-dependent production of superoxide anion, through the production of highly reactive dipeptide thiol cysteinyl-glycine. Cultured THP-1 macrophagic cells, as well as isolated monocytes obtained from healthy donors and differentiated to macrophages in vitro, were investigated as to their expression of GGT and the effects of exposure to crocidolite. The results show that crocidolite asbestos at subtoxic concentrations (50–250 ng/1000 cells) can upregulate GGT expression, which raises the possibility that macrophage-initiated, GSH/GGT-dependent pro-oxidant reactions may participate in the pathogenesis of tissue damage and inflammation consequent to crocidolite intoxication.


2018 ◽  
Vol 6 (7) ◽  
pp. 1105-1117 ◽  
Author(s):  
Kai Dong ◽  
Chunrong Yang ◽  
Yan Yan ◽  
Pengchong Wang ◽  
Ying Sun ◽  
...  

Redox-responsive FSST micelles with good biocompatibility can increase ROS levels in tumor cells and amplify oxidative stress, ultimately inducing apoptosis.


Endocrinology ◽  
2000 ◽  
Vol 141 (7) ◽  
pp. 2518-2525 ◽  
Author(s):  
Christine Duthoit ◽  
Valérie Estienne ◽  
Frédéric Delom ◽  
Josée-Martine Durand-Gorde ◽  
Bernard Mallet ◽  
...  

Here, we studied the fragmentation of the prothyroid hormone, thyroglobulin (Tg), which occurs during thyroid hormone synthesis, a process which involves iodide, thyroperoxidase, and the H2O2-generating system, consisting of glucose and glucose oxidase. Various peptides were found to be immunoreactive to autoantibodies to Tg from patients and monoclonal antibodies directed against the immunodominant region of Tg. The smallest peptide (40 kDa) bore thyroid hormones and was identified at the C-terminal end of the Tg molecule, which shows homologies with acetylcholinesterase. Similar peptides were obtained by performing metal-mediated oxidation of Tg via a Fenton reaction. It was concluded that the oxidative stress induced during hormone synthesis generates free radicals, which, in turn, cleave Tg into immunoreactive peptides.


2016 ◽  
Vol 13 (2) ◽  
pp. 407-413
Author(s):  
Baghdad Science Journal

The oxidative stress is result of unbalancing between oxidants and antioxidants in the body. Hypertension (HT) is a measure of average systolic blood pressure which created by the heart contracting, greater ?140 mmHg or an average diastolic blood pressure, which is the heart fills, of ?equal to 90 mmHg. The study is conducted on 28 female patients with HT from Ibn Al-nafese hospital in addition to 28 female control. The markers measured are albumin, malondialdehyde (MDA) and 8-Hydroxy deoxyguanosine (8-OHdG). Also electrophoresis study on extracted DNA with Fenton reaction was done. Results of this study show there are high significant decrease (p?0.01) in albumin concentration of patient related to control, and there is a high significant increase (p? 0.01) in each MDA and 8-OHdG for patients group in comparison with controls. The Fenton reaction done shows that oxidant has degradation effect on DNA either in two minutes of reaction. It is concluded that oxidative stress in its parameter (albumin) and markers (MDA and 8-OHdG) is main chemical manifestation of group under study. And oxidants produced by Fenton can denature the DNA in vitro.


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